NPASS Compound

Natural Product: NPC44887

Natural Product ID	NPC44887
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	XCVOCJFOQNDTNC-VIVMMSDESA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	9949818
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0002105] Glycosyl compounds [CHEMONTID:0002207] O-glycosyl compounds

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 40 42 0 0 0 0 0 0 0 0999 V2000 -4.1037 1.8580 -1.1980 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4446 0.7387 -0.4451 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.2632 -0.5050 -0.3825 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5862 -1.5236 0.4597 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1196 -1.4564 0.5299 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4800 -0.2161 -0.0159 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2246 0.3617 -1.0532 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1883 -0.5106 -0.4221 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0002 -0.0147 0.0177 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1865 0.9154 0.9909 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3964 1.3065 1.3180 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4862 0.8512 0.7559 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7536 1.2661 1.1040 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8661 0.7434 0.4688 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7600 -0.1945 -0.5185 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4970 -0.6156 -0.8735 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3997 -0.1057 -0.2530 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1460 -0.5251 -0.6069 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0549 -1.3864 -1.5139 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3768 -1.5679 -1.8749 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1309 1.1771 0.8371 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6850 -1.5982 1.8661 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1285 -1.4160 1.7628 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5444 -0.1921 0.0976 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8590 1.8274 -2.2788 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1703 1.8525 -0.9750 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6686 2.8133 -0.7915 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2499 1.0771 0.6060 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4331 -0.9178 -1.4130 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9382 -2.5381 0.1061 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6850 -2.3385 -0.0047 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4501 0.5463 0.7904 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2981 1.3203 1.4848 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8360 2.0150 1.8925 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6490 -0.5861 -0.9983 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7775 -2.4861 -1.7633 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2339 2.1583 1.0463 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3779 -0.7144 2.2312 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0648 -0.4826 2.0315 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1836 -0.9366 -0.0683 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 6 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 16 20 1 0 14 21 1 0 5 22 1 0 4 23 1 0 3 24 1 0 7 2 1 0 18 9 1 0 17 12 1 0 1 25 1 0 1 26 1 0 1 27 1 0 2 28 1 1 3 29 1 6 4 30 1 6 5 31 1 6 6 32 1 1 10 33 1 0 13 34 1 0 15 35 1 0 20 36 1 0 21 37 1 0 22 38 1 0 23 39 1 0 24 40 1 0 M END

Standard InCHIKey	XCVOCJFOQNDTNC-VIVMMSDESA-N
Standard InCHI	InChI=1S/C15H16O9/c1-5-11(18)13(20)14(21)15(23-5)24-9-4-22-8-3-6(16)2-7(17)10(8)12(9)19/h2-5,11,13-18,20-21H,1H3/t5-,11-,13-,14-,15+/m0/s1
SMILES	C[C@H]1[C@@H]([C@@H]([C@@H]([C@H](O1)Oc1coc2cc(cc(c2c1=O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	340.08	Volume:	308.257 ? Van der Waals volume.
Dense:	1.103	LogP:	0.966 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.469 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.596 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	149.82 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	5.0	Rings:	3.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.483	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.993	Fsp³:	0.4
MCE-18:	69.524 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.521	Fluc inhibitor:	0.054 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.631 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.507 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.21	Promiscuous compounds:	0.511

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.191	MDCK Permeability:	-5.233
Pgp-inhibitor:	0.0	Pgp-substrate:	0.739
PAMPA:	0.998 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.084
20% Bioavailability (F20%):	0.226	30% Bioavailability (F30%):	0.757
50% Bioavailability (F50%):	0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.235
Plasma Protein Binding (PPB):	80.803%	Volume Distribution (VD):	-0.189
Fu:	19.828% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.498
OATP1B3 inhibitor:	0.896	BCRP inhibitor:	0.725
BSEP inhibitor:	0.069

ADMET: Metabolism

CYP1A2-inhibitor:	0.072	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.013	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.12
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.005
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.995
HLM stability:	0.392 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

3.102

Half-life (T1/2):

3.896

ADMET: Toxicity

hERG Blockers:	0.052	hERG Blockers (10um):	0.409
Human Hepatotoxicity (H-HT):	0.337	Drug-induced Liver Injury (DILI):	0.361
AMES Toxicity:	0.68	Rat Oral Acute Toxicity:	0.13
Maximum Recommended Daily Dose:	0.298	Skin Sensitization:	0.476
Carcinogencity:	0.211	Eye Corrosion:	0.002
Eye Irritation:	0.885	Respiratory Toxicity:	0.086
Drug-induced Neurotoxicity:	0.008	Ototoxicity:	0.7
Hematotoxicity:	0.06	Drug-induced Nephrotoxicity:	0.105
Genotoxicity:	0.582	RPMI-8226 Immunitoxicity:	0.07
A549 Cytotoxicity:	0.056	Hek293 Cytotoxicity:	0.352
BCF:	0.379 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.048 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.412 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.565 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.3987/COM-96-7609.]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16038566]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	stem	n.a.	PMID[16964757]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18081254]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[23059629]
NPO7132	Smilax glabra	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7132	Smilax glabra	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7132	Smilax glabra	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7132	Smilax glabra	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7132	Smilax glabra	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7132	Smilax glabra	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC44887 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	20581
0.1-0.2	25984
0.2-0.3	2417
0.3-0.4	617
0.4-0.5	195
0.5-0.6	38
0.6-0.7	16
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC268668
0.8226	Intermediate Similarity	NPC78697
0.7188	Intermediate Similarity	NPC262699
0.7188	Intermediate Similarity	NPC131217
0.6528	Remote Similarity	NPC111929
0.6528	Remote Similarity	NPC320283
0.6528	Remote Similarity	NPC41121
0.6301	Remote Similarity	NPC135599
0.6301	Remote Similarity	NPC73855
0.6301	Remote Similarity	NPC113968
0.6301	Remote Similarity	NPC328940
0.6301	Remote Similarity	NPC277174
0.6301	Remote Similarity	NPC606877
0.6216	Remote Similarity	NPC127546
0.6216	Remote Similarity	NPC57625
0.6216	Remote Similarity	NPC173637
0.6216	Remote Similarity	NPC317489
0.6216	Remote Similarity	NPC223424
0.6216	Remote Similarity	NPC600591
0.6133	Remote Similarity	NPC265530
0.5897	Remote Similarity	NPC219904
0.575	Remote Similarity	NPC223747
0.5412	Remote Similarity	NPC173582
0.5412	Remote Similarity	NPC265885
0.5412	Remote Similarity	NPC181465
0.5412	Remote Similarity	NPC215710
0.5412	Remote Similarity	NPC473438
0.5412	Remote Similarity	NPC253788
0.5385	Remote Similarity	NPC77672
0.5385	Remote Similarity	NPC133671
0.5385	Remote Similarity	NPC135391
0.5385	Remote Similarity	NPC78263
0.5385	Remote Similarity	NPC250069
0.5375	Remote Similarity	NPC138540
0.5316	Remote Similarity	NPC156457
0.5233	Remote Similarity	NPC39834
0.519	Remote Similarity	NPC19388
0.519	Remote Similarity	NPC240431
0.519	Remote Similarity	NPC249281
0.519	Remote Similarity	NPC55786
0.519	Remote Similarity	NPC348541
0.5172	Remote Similarity	NPC203259
0.5172	Remote Similarity	NPC33054
0.5172	Remote Similarity	NPC176740
0.5172	Remote Similarity	NPC471725
0.5172	Remote Similarity	NPC134532
0.5172	Remote Similarity	NPC602582
0.5125	Remote Similarity	NPC145038
0.5125	Remote Similarity	NPC56077
0.5125	Remote Similarity	NPC281131
0.5125	Remote Similarity	NPC64305
0.5125	Remote Similarity	NPC253662
0.5125	Remote Similarity	NPC179950
0.5125	Remote Similarity	NPC88789
0.5125	Remote Similarity	NPC491374
0.5122	Remote Similarity	NPC481043
0.5119	Remote Similarity	NPC476215
0.5062	Remote Similarity	NPC46420

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC44887 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5066
0.1-0.2	4030
0.2-0.3	42
0.3-0.4	11
0.4-0.5	0
0.5-0.6	1
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.5172	Remote Similarity	NPD6797	Phase 2

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data